Project Summary Psychostimulant addiction poses a significant burden on our society, afflicting millions of Americans, and has proven difficult to treat, possibly because of the complexity of the disorder. Many behavioral procedures have been developed to model the addiction process in several species including non-human primates and rats. The neuropeptide orexin, made exclusively in the hypothalamus, has been shown to play an important role in both motivational responding for cocaine and the association of drug reward with predictive cues. The goal of the present proposal is to better understand the importance of this system in the progression of the addiction process. Two different behavioral procedures will be used that produce phenotypes associated with increased drug seeking in rats. An array of techniques will be employed to understand the function of the orexin system in rats experiencing these behavioral procedures. These techniques include histology and immunohistochemistry, intra-cranial pharmacology, and administration of vivo-morpholinos to suppress orexin protein expression. Using these techniques to understand the role the orexin system plays in these behavioral procedures will greatly increase our understanding of the underlying neurobiology associated with the progression of the addiction process. This research will identify a number of targets for potential pharmacological treatments. These are all new techniques for me, and learning these modern neuroscience methods will train me in how to examine and manipulate specific brain circuits to identify their roles in the addiction process. This training will be critical to my future development as a research neuroscientist in addiction.